Project Summary Orientation selectivity, a fundamental feature observed throughout the early visual system, is first computed in the retina by orientation selective ganglion cells (OSGCs). Recent work has reported diverse mechanisms underlying On and Off OSGCs, yet less is known about the On-Off type. My preliminary calcium imaging data suggests that On-Off OSGCs are a major OSGC subtype in the mouse retina and they are sensitive to GABAA receptor antagonists. This proposal aims to determine the synaptic mechanisms underlying the orientation selectivity of On-Off OSGCs in the mouse retina and their central projection patterns. The lack of molecular markers for OSGCs has limited a mechanistic understand of orientation selectivity in the mammalian retina. In Aim 1, we will perform calcium imaging of RGCs to screen for On-Off OSGCs and target them for single-cell recordings. Additionally, we will use pharmacology and ?-subunit specific manipulations of GABAA receptors on RGCs to determine the involvement of specific synapses in orientation selectivity. In Aim 2, we will identify the projection patterns of On-Off OSGCs to dorsal LGN using viral retrograde tracers and transgenic labeling. Learning to perform whole-cell patch-clamp recordings and retrograde tracer injections are major training goals of this grant. Results from this work will yield a mechanistic understanding of retinal orientation selectivity and provide a link between this retinal feature selectivity and higher visual processing in the thalamocortical pathway.